Theresa May's Brexit strategy has been dealt a devastating blow after the House of Commons rejected her EU Withdrawal Agreement by an overwhelming majority for the second time.

MPs voted by 391 to 242 against the deal, despite the Prime Minister’s assurance that new agreements reached with Jean-Claude Juncker in Strasbourg would ensure the UK cannot be trapped in the controversial backstop arrangement indefinitely.

Although the 149 margin was reduced from the record 230-vote defeat of the first “meaningful vote” in January, Mrs May was left far adrift from a majority with just 17 days to go to the scheduled date of Brexit on March 29.

European Commission president Mr Juncker had already warned that if MPs turned down the package agreed in Strasbourg on Monday, there would be “no third chance” to renegotiate.

In line with a promise set out by Mrs May last month, MPs are now due to vote on Wednesday on whether they are willing for the UK to leave the EU without a deal on March 29.

If they reject no-deal as most Westminster observers expect, a third vote will follow - probably on Thursday - on authorising Mrs May to request an extension of the two-year Article 50 negotiation process.

An extension requires the unanimous agreement of all 27 remaining member states, and Mr Juncker has warned that it cannot stretch beyond May 23 unless the UK takes part in the European Parliament elections starting on that date.

Cabinet gave its approval to Mrs May’s package at an early-morning meeting in 10 Downing Street which ended with the PM telling colleagues: “Today is the day. Let’s get this done.”

But the momentum moved sharply against the Prime Minister shortly afterwards, as Attorney General Geoffrey Cox released formal legal advice that the changes secured by Mrs May “reduce the risk” that the backstop will be permanent, but do not remove it altogether.

The Star Chamber of lawyers convened by the Brexit-backing European Research Group declared that three new documents agreed in Strasbourg failed to deliver the legally-binding changes demanded by the Commons.

And the Democratic Unionist Party - which props up Mrs May’s minority administration in the Commons - said its 10 MPs would vote against the latest deal as “sufficient progress has not been achieved at this time”.

The Prime Minister, battling a croaky voice and with husband Philip watching from the Commons gallery, warned MPs that “Brexit could be lost” if they gave her deal the thumbs-down again.

But she met a wall of hostility from opposition parties, while only a handful of the 118 Tories who rebelled in January said they would switch sides to back her.

Shadow Brexit secretary Sir Keir Starmer said that “no significant changes” had been secured in two months of negotiations and the Government’s strategy was “in tatters”.

Brexit figurehead and former foreign secretary Boris Johnson told the Commons that Mrs May and Mr Cox had “sowed an apron of fig leaves that does nothing to conceal the embarrassment and indignity of the UK.”

Labour leader Jeremy Corbyn told the Commons: “After three months of running down the clock the Prime Minister has, despite very extensive delays, achieved not a single change to the Withdrawal Agreement.

“Not one single word has changed. In terms of the substance, literally, nothing has changed.”

Charles Walker, vice chairman of the 1922 Committee of backbench Tory MPs, warned that defeat in the second “meaningful vote” on Tuesday evening would lead to a general election.

He told BBC Radio 4’s World At One: “If it doesn’t go through tonight, as sure as night follows day, there will be a general election within a matter of days or weeks.

“It is not sustainable, the current situation in Parliament.”

Following the defeat Mrs May told the House of Commons that she will grant a free vote to Conservative MPs in a vote on Wednesday on whether the UK should leave the EU without a deal on March 29.